Discovery of a Pathogenic NME5 Variant Underlying Acephalic Spermatozoa Syndrome

NME5 (c.163delA, p.Ser55Valfs*16, homozygous)

Homozygous frameshift (LOF) + functional characterization (ultrastructure, immunofluorescence, spermatogenic expression)

The authors identify a novel homozygous frameshift variant in NME5 in a patient with ASS. Functional analyses confirm loss of protein and reveal ultrastructural abnormalities of the head–tail coupling apparatus and mitochondrial sheath, with near-complete absence of SPATA6. ICSI led to a successful pregnancy. First demonstration of the causal role of NME5 in human ASS.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

NME5 joins the list of monogenic ASS genes with a complete package: identification, functional proof, clinical implications (successful ICSI). To be added to syndromic male infertility panels.

new gene +3; biallelic +2; full functional +2; isolated case +0; clinical impact (ICSI) +1; Clin Genet journal +1